NZ565003A

NZ565003A - Composition for treating skin lesions

Info

Publication number: NZ565003A
Application number: NZ565003A
Authority: NZ
Inventors: John Spurge
Original assignee: Dynamiclear Pty Ltd
Priority date: 2005-06-20
Filing date: 2006-06-20
Publication date: 2011-11-25
Also published as: WO2006135965A1; EP1906978B1; CA2613297C; EP1906978A4; US20100278936A1; JP2008543885A; CN101203232A; ES2396719T3; ZA200800006B; CA2613297A1; US9107811B2; BRPI0613824A2; EP1906978A1; HK1115328A1

Abstract

A process of producing an anti-viral topical formulation comprising an amount of a copper compound sufficient to provide copper ion concentration of 1% to 5% w/w as an active trace metal in an aqueous herbal base for treatment of viral associated skin and/or mucosal membrane lesions in a subject is disclosed, wherein said process comprises: forming a copper solution from a copper compound;adding glycerin to the copper solution;adding an aqueous herbal extract to the copper solution;bringing the solution to a desired concentration using water;optionally adding a preservative andoptionally filtering to remove any sediment. A composition for topical treatment of viral associated skin and/or mucosal membrane lesions is also disclosed, which comprises an effective amount of: a copper compound sufficient to provide copper ion concentration of 1 % to 5% w/w (wherein the preferred copper compound is copper sulphate, copper chloride or copper salicylate); and hypericum perforatum extract.

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number 565003 WO 2006/135965 PCT/AU2006/000863 1 COMPOSITION FOR TREATING SKIN LESIONS Technical Field The present invention relates to a composition for the treatment of skin lesions 5 and use of the composition. In particular, the invention relates to compositions for treatment of skin lesions associated with viral infections, such as Herpes simplex. Background Art Herpes is a sexually transmitted disease (STD) caused by the herpes simplex 10 virus (HSV). There are two types of HSV; Herpes Simplex 1 (HSV1) and Herpes Simplex 2 (HSV2). HSV1 or mouth herpes is commonly in the form of cold sores on and around the mouth. HSV2 or genital herpes is a much more intense strain commonly found on the genitals. However both types can be found on the mouth or genital areas. It is possible 15 to be infected by both HSV1 and HSV2. Being infected by one particular strain does not make you immune to another. Recurrent outbreaks of the Herpes virus generally follow a staged progression. The stages are easily identifiable and include prodrome, vesicles, ulceration, crust and healing. Prodrome is generally a short period of tingling, itching, numbness or burning 20 with no visible sign of an outbreak. Vesicles are the formation of one or more fluid-filled blisters, often in a cluster and usually surrounded by sore, red skin. The ulceration stage is when the blisters open to form painful ulcers or open sores. At the edge of the sore, a soft or hard yellow crust begins to appear. Ulcers and painful, sore, red skin persist through this stage. At the crust stage, weeping sores or ulcers become 25 completely covered by a crust or scab. No ulcers or blisters are present. The healing process is manifested by disappearance of the crust, swelling, pain and itching. Skin eruptions due to viral infection, especially Herpes viruses, generally have a normal infective course that lasts from 10 to 60 days depending on the exact causative species and anatomical location of the infection. 30 After the initial outbreak, the virus usually lies dormant in the skin or in nerve tissue (latent state) until something triggers another eruption or site infection. When the virus reactivates, it characteristically causes a sore at the site where it first entered the body. Often the trigger is unknown, but in some people overexposure to sunlight, fever, WO 2006/135965 PCT/AU2006/000863 2 physical or emotional stress, hormonal changes such as pregnancy or menstruation, or certain foods and drugs seem to reactivate the virus. Genital herpes on the other hand is generally considered to be sexually transmitted. An estimated 40 million people of the world population have genital herpes 5 which makes it a chronic viral infection. About 500,000 people get new symptomatic herpes each year and there are even more people without symptoms. It has been estimated that about 20% of the world population have genital herpes and 90% have oral herpes (cold sores). To date, there is neither a vaccine to prevent the Herpes infection, nor any way 10 to eliminate the virus from the body. The fact that the herpes virus retreats into the nervous system makes it extremely difficult to eliminate completely. Previous treatments for herpes virus infections have included the topical application of 5% by weight of acyclovir (Zovirax®), oral administration of valacyclovir HCI (Valtrex®) and laser treatments such as Lectroject®. Each of these treatments is 15 expensive to the patient and the effectiveness is quite slow and often painful. Side effects such as headache and nausea are not uncommon when using repeated applications of acyclovir, whilst the Lectroject® laser method of treating herpes increases the possibility of scar tissue formation. Accordingly, there remains a need for an effective treatment of skin lesions, and 20 in particular, skin lesions associated with viral infections such as Herpes. Most herpes medications act to "suppress" the virus inside the body in order to reduce outbreaks. In contrast,, the present inventors have developed a composition which works by substantially eliminating the virus on direct contact at the outbreak site which accelerates the recovery time of the viral outbreaks and reduces the inconvenience and 25 embarrassment of the condition. Summary of Invention The present invention generally provides topical preparations and methods for treatment of skin and mucosal membrane lesions associated with microibial infections 30 such as Herpes simplex. In a first aspect, the present invention provides a composition for topical treatment of skin and mucosal membrane lesions comprising a synergistic combination of: a copper compound; and WO 2006/135965 PCT/AU2006/000863 hypericum perforatum extract. The composition may further comprise a skin protectant. The composition may further comprise a preservative. Preferably, the preservative is Germall Plus (Diazolidinyl Urea and lodopropyynyl Butylcarbamate from 5 ISP Sutton Laboratories). Preferably, the composition comprises: (a) about 5 - 9% (w/w) copper compound ; (b) about 0.05 to 0.15% (v/v) hypericum perforatum extract; (c) about 1 to 5% (w/w) a skin protectant; 10 (d) optionally about 0.1 to 0.3% (w/w) preservative; and (e) balance water. Preferably the copper compound is in the form of copper sulphate, copper chloride or copper salicylate. More preferably, the copper compound is in the form of copper sulphate, and more preferably copper sulphate pentahydrate. 15 Preferably, the copper compound is provided as copper sulphate at about 5 - 9% (w/w), more preferably as copper sulphate pentahydrate. Typically, the copper compound provides copper ions at a concentration of about 1 - 5% (w/w). Preferably, the copper sulphate is at a concentration of about 5% by weight. 20 More preferably, the copper sulphate pentahydrate is at a concentration of about 7.8% by weight. Hypericum perforatum is plant extract (flower extract) and can be obtained or prepared by means of solvent (ethanol) extraction. Preferably, the hypericum perforatum is at a concentration of about 0.1 % by volume. 25 The composition may further comprise aloe vera. Aloe vera is obtained from the Aloe barbadenisis plant which is a cactus-like plant belonging to the Lilly family and can be obtained or prepared by means of solvent (ethanol) extraction. Preferably, the aloe vera is at a concentration of about 1.0% by weight. In one embodiment, the composition may further comprise sodium ascorbate. 30 Preferably the sodium ascorbate is at a concentration of about 3-10% (w/w). In another embodiment, the composition may further comprise hydrogen peroxide. Preferably, the hydrogen peroxide is at a concentration of about 3-10% (w/w). WO 2006/135965 PCT/AU2006/000863 Preferably, the skin protectant is selected from the group consisting of glycerin or sorbitol. More preferably, the skin protectant is glycerin. The skin protectant is preferably used at a concentration of about 5.0% by weight. Preferably, the water is at a concentration of about 60% to 85% by weight. 5 Preferably, the composition is in a form selected from a cream, lotion, emollient, gel, or emulsion. In a second aspect, the present invention provides a method of treating or preventing skin lesions comprising applying to the lesion a therapeutically effective amount of a composition according to the first aspect of the present invention. 10 In a third aspect, the present invention provides use of a composition according to the first aspect of the present invention for the manufacture of a medicament for the treatment or prevention of viral associated skin or mucosal membrane lesions. Preferably, the composition is applied once per viral infection. Preferably, the composition is applied to a visible and mature lesion. 15 In one preferred form, the lesions are located on or around the mouth area. In another preferred form, the lesions are located on or around the genital region of a subject. Preferably, the lesions are associated with a skin infection. More preferably, the skin infection may be associated with a bacterial, fungal or viral infection. 20 Preferably the lesions are associated with a viral infection. More preferably, the viral infection is selected from Herpes Simplex virus, Herpes Zoster virus, Polio virus, Shingles-associated viruses, Varicella Zoster virus, Chicken pox-associated viruses or Human Immunodeficiency virus. Preferably, the virus is Herpes Simplex virus. Preferably, the lesions are associated with a fungal infection. More preferably, 25 the fungal infection is tinea. The carriers, excipients and/or diluents utilised should be acceptable for human or veterinary applications. Such carriers, excipients and/or diluents are well-known to those skilled in the art. Carriers and/or diluents suitable for use include any and all solvents, dispersion media, aqueous solutions, coatings, antibacterial and antifungal 30 agents, isotonic and absorption delaying agents, and the like. Except insofar as any conventional media or agent is incompatible with the active ingredient, use thereof in the composition is contemplated. Supplementary active ingredients can also be incorporated into the compositions. WO 2006/135965 PCT/AU2006/000863 In a fourth aspect, the present invention provides a process of producing a composition for the treatment of viral associated skin and mucosal membrane lesions, the process comprising: forming a copper solution from a copper compound ; 5 optionally adding glycerin to the copper solution; adding hypericum perforatum to the copper solution; bringing the solution to a desired concentration using water; optionally adding a preservative; and optionally filtering to remove any sediment. 10 Throughout this specification, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. 15 Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed in Australia before the priority date of 20 the invention disclosed in this application. In order that the present invention may be more clearly understood, preferred forms will be described with reference to the following examples. Mode(s) for Carrying Out the Invention 25 Previous topical medications have used high concentrations of copper sulphate, some as high as 10 % by weight. High concentrations of copper have been found to cause blood poisoning which can be potentially fatal. In contrast, the present inventors have surprisingly shown that a copper compound used at a concentration of 5-9% by weight in combination with 0.05 to 0.15% by weight of hypericum perforatum extract 30 provides a synergistic antiviral effect in the treatment of skin lesions. Use of a lower concentration of copper results in the composition being safe, providing an effective dose to be used topically, even on open wounds. Prior art uses indicate that it is WO 2006/135965 PCT/AU2006/000863 necessary to use high concentrations of copper sulphate to provide adequate anti-viral activity. The present inventors have found that the combination of copper compound and hypericum perforatum extract according to the present invention is significantly more 5 effective and has an antimicrobial affect at lower concentrations than the use of the copper compound or hypericum perforatum extract alone. It has now been found and is the subject of the present invention that a composition comprising a synergistic combination of copper, preferably in the form of copper sulphate pentahydrate and a herbal antiviral agent such as hypericum 10 perforatum is effective in dramatically reducing the healing time of viruses such as Herpes lesions, stopping the normal progression of the viral outbreak from the stage at which the initial outbreak occurred, and also in reducing further recurrences of the virus. The composition of the present invention is a copper^based solution with copper as the active trace metal in an aqueous herbal base. 15 The present invention relates to the use of chemically supplemented compositions for the treatment of viral associated skin and mucosal membrane lesions. The present inventors have found that a combination of copper, preferably in the form of copper sulphate and the herbal antiviral agent hypericum perforatum extract, provides a synergistic antiviral effect in the treatment of skin lesions. In this aspect, there is 20 provided a composition and method for treating viral associated skin and/or oral mucosa lesions. The method of which comprises administration to the patient an effective amount of a composition preferably comprising copper sulphate and hypericum perforatum. Whilst it is not intended that the present invention should be restricted in any way 25 by a theoretical explanation of the mode of action of copper and hypericum perforatum in accordance with the invention, it is presently believed that these active ingredients may exert their antiviral and healing effect by the composition being slightly acidic which results in it being corrosive to the virus. Furthermore, the process of producing the composition results in the composition possessing both an acid group and sulfur 30 molecule which .assists in the penetration of the composition through the protective capsule of the herpes virus and allows for the direct contact and subsequent destruction of the virus. The compositions of the present invention are those recognised in the pharmaceutical arts as being suitable for topical application and include, without WO 2006/135965 PCT/AU2006/000863 7 intended limitation, creams, lotions, liquid emulsions, gels, aqueous solutions and the like. The present compositions preferably include copper sulphate pentahydrate in from about 5 to 9, preferably 7.8% by weight or copper ion from about 1 to 5%, (equivalent to about 3 to 7% copper sulphate), preferably 5% by weight, glycerin in from about 5% by 5 weight and hypericum perforatum extract in from about 0.05 to 0.15%, preferably about 0.1 % by weight. The careful selection of the components of the present composition has provided an optimal antiviral effect that has produced unexpectedly enhanced results. In addition to the enhanced therapeutic effect, the subject composition is also advantageous in that it is safe and has no known side-effects, unlike many previous 10 copper-based preparations. The composition can also be safely used for veterinary purposes. The skin protectant forms a barrier over the skin surface to protect against irritation due to touching, rubbing etc. The skin protectant also provides a protective barrier over the lesion, preventing loss of the active ingredient to the action of saliva. In 15 a preferred embodiment, the skin protectant is in the form of glycerin. In addition to the foregoing ingredients, the composition of the present invention may contain other ingredients such as are recognised by those skilled in the pharmaceutical industry as being typically present in such formulations. These include, without limitation, one or more preservatives, osmotic regulators, thickeners, flavours, 20 fragrances, emollients, humectants, colorants, pigments and the like. It would be clear to the skilled addressee that the compounding of the composition of the present invention will be carried out utilising some or all of these ingredients depending on the area of application and intended use. For example, for a preparation intended for application in or around the mouth, it may be necessary to add flavours to mask the 25 taste of the essential ingredients. Although best long term results are achieved by applying the composition to a visible and mature lesion, patients have reported great success in preventing outbreaks by applying the composition in the early stages. This can include applying the composition topically to the affected area as the first sign of symptoms such as itching, 30 tingling, redness or inflammation. EXAMPLES Example 1 An aqueous solution was prepared from formula 1 given below. WO 2006/135965 8 PCT/AU2006/000863 10 15 Formula 1 Components Assay as copper sulphate pentahydrate (CuS04.5H20) (Assay equivalent copper sulphate anhydrous (CuS04) Glycerin (Glycerol) Hypericum perforatum Germall Plus (preservative) Water Purified Formula 2 Components Assay as copper sulphate Glycerin (Glycerol) Hypericum perforatum Germall Plus (preservative) Water Purified Typical Amount 7.80% w/w max 5.0% w/w max 5.0% w/w max 0.1% v/v max 0.3% v/v max Balance Typical Amount 9% w/w max 5% w/w max 0.15% v/v max 0.3% v/v max Balance Formula 3 20 Components Typical Amount Assay as copper sulphate 5% w/w max Glycerin (Glycerol) 1 % w/w max Hypericum perforatum 0.05% v/v max Germall Plus (preservative) 0.1 % v/v max 25 Water Purified Balance WO 2006/135965 PCT/AU2006/000863 Formula 4 Components Assay as copper chloride Glycerin (Glycerol) Hypericum perforatum Germall Plus (preservative) Water Purified Typical Amount 9% w/w max 3.0% w/w max 0.2% v/v max 0.2% v/v max Balance Formula 5 10 Components Assay as copper chloride Glycerin (Glycerol) Hypericum perforatum Germall Plus (preservative) 15 Water Purified Typical Amount 9% w/w max 3.0% w/w max 0.2% v/v max 0.2% v/v max Balance Formula 6 Components Assay as copper salicylate 20 Glycerin (Glycerol) Hypericum perforatum Germall Plus (preservative) Water Purified Typical Amount 9% w/w max 3.0% w/w max 0.2% v/v max 0.2% v/v max Balance 25 The solution was prepared by filling a suitable vessel with about 60% distilled water. Copper compound was added to the water with continuous stirring. Mixing of the solution continued for 10 minutes or until the copper was fully dissolved. Glycerin was added to the solution and mixed for a few minutes. Hypericum perforatum was gradually added to the solution with continuous mixing. The solution was then brought 30 to final weight by the slow addition of the required amount of water with continuous WO 2006/135965 PCT/AU2006/000863 10 blending for about 10 minutes. Preservative Germall Plus was added to the solution and the solution was then allowed to stand for 12 to 15 hours to stabilise. The solution was then filtered to remove the sediment and packaged. 5 Example 2 Treatment of Herpes Simplex Patients with the Composition The solution prepared in Example 1 was tested for its effectiveness against Herpes virus. In order to determine the effectiveness of the composition in reducing the healing time of the Herpes outbreak and/or reducing the recurrence of the outbreaks, 51 10 patients were observed. Of the 51 patients treated with the composition, 34 suffered from mouth lesions associated with Herpes Simplex virus 1 and 19 suffered from genital lesions associated with Herpes Simplex virus 2 (2 patients suffered from both mouth and genital lesions). Following topical application of the composition to the area of the viral-associated lesion, 15 38 of the 51 patients reported a dramatic reduction in the healing time of the lesion (with scab formation occurring within 24 hours) and 47 of the 51 patients reported a reduced recurrence of the viral outbreaks. All patients reported a substantial reduction in pain and discomfort associated with the lesions following application of the composition. 20 Example 3 Prospective, Comparative Study to Evaluate the Safety, Tolerability and Efficacy of the Composition in Patients Suffering from Herpes Simplex Infection (HSV1 and HSV2) The trial enrolled 150 herpes simplex patients (HSV 1 & HSV 2) who have active lesions on external genitalia and skin, between the ages of 18 and 55 years. Subjects 25 were randomized into two groups (A and B). Subjects in Group A topically applied a composition as defined in Example 1, transferring 2-4 drops (depending upon the affected area) to a wet cotton swab (enough to saturate it) on the affected part only once at clinic. Subjects in Group B topically applied 0.5 -1.5 grams of the comparator article 30 (Acyclovir 5% cream) twice daily (once in the morning and once at night) to cover the affected area for 7 days. The patients in Group A presented for efficacy & safety assessments on Day 2, Day 3, Day 8 and Day 14. Group B patients presented on Day 3 and Day 8 for efficacy evaluation and on Day 14 for follow up. Patients also recorded his / her assessment of symptoms on 35 a patient diary from Day 1 to Day 14. </div>

Claims

<div class="application article clearfix printTableText" id="claims"> WO 2006/135965 PCT/AU2006/000863 11 Safety were evaluated by adverse event reports throughout the study. Hematology and clinical chemistry labs, urinalysis, and physical exam of basic systems were obtained at initial screening and Day 14 (end of study) visits. Treatment was be initiated on Day 1, pending the results of laboratory investigations. The patient was withdrawn 5 immediately from the study if the results show abnormal values in laboratory investigation reports. Efficacy endpoint assessments shall be completed to determine time to > 50% crusting/scabbing or healed ulcer within 48 hours. Cutaneous assessments include disappearance of Erythema, Crust/Scab formation in ulcers, disappearance of pain and 10 disappearance of itching and burning sensation. Cutaneous efficacy assessments shall be performed at each visit on Day 2, Day 3 and Day 8 in Group A while in Group B it were performed on Day 3 and Day 8 or until 100% crusting was observed. Local cutaneous tolerability shall be evaluated with assessments of erythema, 15 induration and stinging sensation on Day 1, Day 2, Day 3 and Day 8 in Group A and on Day 3 and Day 8 in Group B or until 100% crusting is observed. The foregoing case studies demonstrated the enhanced effectiveness of the composition in accordance with the present invention in the treatment of skin and mucosal membrane lesions caused by Herpes infections. 20 It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific examples without departing from the spirit or scope of the invention as broadly described. The present examples are, therefore, to be considered in all respects as illustrative and not restrictive. RECEIVED at IPONZ on 10 October 2011 12 THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

1. A process of producing an anti-viral aqueous herbal formulation for topical treatment of viral associated skin and/or mucosal membrane lesions in a subject wherein said| formulation comprises an amount of a copper compound sufficient to provide copper ion concentration of 1% to 5% w/w as an active trace metal, and wherein said process comprises: forming a copper solution from a copper compound; adding glycerin to the copper solution; adding an aqueous herbal extract to the copp# solution; bringing the solution to a desired concentration using water; optionally adding a preservative; and optionally filtering to remove any Sediment.

2. A process of producing an anti-viral topical formulation comprising an amount of a copper compound sufficient to provide copper ion concentration of 1% to 5% w/w as an active trace metal in an aqueous herbal base for treatment of viral associated skin and/or mucosal membrane lesions in a subject, wherein said process comprises: forming a copper solution from a copper compound; adding glycerin to the copper solution; adding an aqueous herbal extract to the copper solution; bringing the solution to a desired concentration using water; optionally adding a preservative; and optionally filtering to remove any sediment.

3. The process of claim 2, wherein the base is a cream, lotion, liquid emulsion, gel or aqueous solution.

4. The process according to any one of claims 1 to 3, wherein the copper compound provides copper ion at a concentration of 5% w/w of the formulation.

5. The process according to any one of claims 1 to 4, wherein the formulation comprises an amount of a copper compound at a concentration in the range of 5% to 9% w/w of the formulation. RECEIVED at IPONZ on 10 October 2011 13

6. The process according to any one of claims 1 to 5; wherein the copper compound is selected from the group consisting of copper sulphate, copper chloride or copper salicylate.

7. The process according to any one of claims i to 6, wherein the copper compound is in the form of copper sulphate.

8. The process according to claim 7, wherein the copper sulphate is copper sulphate pentahydrate.

9. The process according to claim 7 or claim 8, wherein the copper sulphate is provided at a concentration of 7.8% (w/w) of the formulation.

10. The process according to claim 7, wherein the copper sulphate is copper sulphate anhydrous.

11. The process according to any one of claims 1 to 8 or claim 10, wherein said formulation comprises up to 7.8% w/w copper sulphate pentahydrate and/or up to 5.0% w/w copper sulphate anhydrous.

12. The process according to any bne of claims 1 to 6 or claim 10, wherein the formulation comprises up to 9% w/w copper chloride or up to 9% w/w copper salicylate.

13. The process according to any one of claims 1 to 12, further comprising adding aloe vera to the solution.

14. The process of claim 13, further comprising adding aloe vera at a concentration of 1% w/w of the final formulation.

15. The process according to any one of claims 1 to 14, further comprising adding sodium ascorbate to the solution.

16. The process of claim 15, comprising addining sodium ascorbate at a concentration of 3% to 10% w/w of the final formulation.

17. The process according to any one of claims 1 to 16, further comprising adding hydrogen peroxide to the solution. RECEIVED at IPONZ on 10 October 2011 14

18. The process of claim 17, comprising adding hydrogen peroxide at a concentration of 3% to 10% w/w of the final formulation.

19. The process according to any one of claims 1 to 18 further comprising adding a a skin protectant to the solution.

20. The process of claim 19, comprising adding a skin protectant at a concentration of 1% to 5% w/w of the final formulation.

21. The process of claim 19 or 20, wherein the skin protectant is glycerin.

22. The process according to any one of claims 1 to 21, comprising adding to the solution any one or more of a preservative, osmotic regulator, thickener, flavor, fragrance, emollient, humectant, colorant, and/or pigment.

23. The process of claim 22, wherein the preservative is Germall Plus/

24. The process of claim 22 or claim 23, comprising adding a preservative at an amount of 0.1% to 0.3% w/w of the final formulation.

25. The process according to any one of claims 1 to 24, further comprising adding a pharmaceutical^ acceptable carrier, excipient and/or diluent.

26. The process according to any one of claims 1 to 25, wherein the skin and/or mucosal membrane lesion(s) are associated with an infection by a virus selected from the group consisting of Herpes Simplex virus, Herpes Zoster virus, Polio virus, Shingles-associated viruses, Varicella Zoster virus, Chicken pox-associated viruses or Human Immunodeficiency virus.

27. The process according to any one of claims 1 to 26, wherein the skin and/or mucosal membrane lesion(s) are associated with an infection by a Herpes Simplex virus.

28. A composition for topical treatment of viral associated skin and/or mucosal membrane lesions comprising an effective amount of: RECEIVED at IPONZ on 10 October 2011 15 a copper compound sufficient to provide copper ion concentration of 1% to 5% ;w/w; . : ■"! I-'/, 'V. and hypericum perforatum extract.

29. The composition of claim 28, wherein the composition comprises a copper compound at a concentration in the fange of 5% to 9% w/w.

30. The formulation' accofclihg w claim or^laim 29, wherein the copper compound provides copper ion at a concentration of 5% w/w of the formulation.

31. The composition according to any one of claims 28 to 30, wherein the copper compound is copper sulphate, copper chloride or copper salicylate.

32. The composition according to claim 31, wherein the copper compound is copper sulphate. -

33. The comjsosltion according to elaim 32, wherein the copper sulphate is copper sulphate pentahydrate .

34. The composition according to claim 32 or claim 33, wherein the copper sulphate is provided at a concentration of 7.8% w/w of the formulation.

35. The composition according to claim 32, wherein the copper sulphate is copper sulphate anhydrous.

36. The composition according to any one of claims 28 to 33 or claim 35, wherein the formulation comprises up to 7*8% w/w copper sulphate pentahydrate and/or up to 5.0% w/w copper sulphate anhydrous.;

37. The composition according to any one of claims 28 to 33, wherein the composition comprises up to 9% w/w copper chloride or up to 9% w/w copper salicylate.;

38. The composition according to any one of claims 28 to 37, wherein the hypericum perforatum extract is at a concentration range of 0.05% to 0.15% w/w of the composition.;RECEIVED at IPONZ on 10 October 2011;16;

39. The composition according to any one of claims 28 to 37, wherein the hypericum perforatum extract is at a concentration of up to 0.2% v/v of the composition.;

40. The composition according to any one of claims 28 to 39, further comprising a skin protectant.;

41. The composition of claim 40, wherein the skin protectant is at a concentration of 1% to 5% w/w. ^;

42. The composition of claim 40 or claim 41, wherein the skin protectant is glycerin.;

43. The composition according to any one of claims 28 to 42, further comprising any one or more of a preservative, osmotic regulator, thickener, flavor, fragrance, emollient, humectant, colorant, or pigment;

44. The composition of claim 43, wherein the preservative is Germall Plus.;

45. The composition of claim 43 or claim 44, comprising 0.1% to 0.3% w/w preservative.;

46. The composition according to any one of claims 28 to 45, further comprising aloe vera.;

47. The composition of claim 46, wherein the composition comprises aloe vera at a concentration of 1% w/w of the composition.;

48. The composition according to any one of claims 28 to 47, further comprising sodium ascorbate.;

49. The composition of claim 48, wherein the composition comprises sodium ascorbate at a concentration of 3% to 10% w/w of the composition.;

50. The composition according any one of claims 28 to 49, further comprising hydrogen peroxide.;RECEIVED at IPONZ on 10 October 2011;17;

51. The composition of claim 50, wherein the composition comprises hydrogen peroxide at a concentration of 3% td 10% w/w of the composition.;

52. The composition according to any one of claims 28 to 51, wherein the composition further comprises a pharmaceutically acceptable carrier, excipient and/or diluent.;

53. The composition according to any one of claims 28 to 52, wherein the composition is in the form of a cream, lotion, emollient, gel or emulsion.;

54. The composition according to any one of claims 28 to 53, wherein the skin and/or mucosal membrane lesion(s) are associated with an infection by a virus selected from the group consisting of Herpes Simplex virus, Herpes Zoster virus, Polio virus, Shingles-associated viruses, Varicella Zoster virus, Chicken pox-associated viruses or Human Immunodeficiency virus.;

55. The composition according to any one of claims 28 to 53, wherein the skin and/or mucosal membrane lesion(s) are associated with an infection by a Herpes Simplex virus.;

56. A process of producing a composition according to any one of claims 28 to 55, the process comprising:;forming a copper solution from a copper compound;;adding glycerin to the copper solution;;adding hypericum perforatum to the copper solution;;bringing the solution to a desired concentration using water;;optionally adding a preservative; and optionally filtering to remove any sediment.;

57. Use of a herbal formulation comprising an amount of copper salt as an active trace metal in the manufacture of a medicament for the topical treatment or prevention of viral associated skin and/or mucosal membrane lesions.;

58. Use of a formulation comprising an amount of copper salt as an active trace metal in an aqueous herbal base in the manufacture of a medicament for the topical treatment or prevention of viraJ associated skin and/or mucosal membrane lesions.;RECEIVED at IPONZ on 10 October 2011;18;

59. The use of according to any one of claims 57 or 58, wherein the formulation comprises copper salt at a concentration of 5% to 9% w/w of the formulation.;

60. The use according to claim 58 or claim 59, wherein the base is a cream, lotion, liquid emulsion, gel or aqueous solution. <;

61. The use according to any one of claims 57 to 60, wherein the copper salt provides copper ion concentration at a range of 1% to 5% w/w of the formulation.;

62. The use according to claim 61, wherein the copper salt provides copper ion at a concentration of 5% w/w of the formulation.;

63. The use according to any one of claims 57 to 62, wherein the copper salt is selected from the group consisting of copper sulphate, copper chloride or copper salicylate.;

64. The use according to any one of claims 57 to 63, wherein the copper salt is in the form of copper sulphate.;

65. The use according to claim 64, wherein the copper sulphate is copper sulphate pentahydrate.;

66. The use according to claim 65, wherein the copper sulphate is provided at a concentration of 7.8% (w/w) of the formulation.;

67. The use according to claim 66, wherein the copper sulphate is copper sulphate anhydrous.;

68. The use according to any one of claims 57 to 65 or claim 67, wherein said formulation comprises up to 7.8% w/w copper sulphate pentahydrate and/or up to 5.0% w/w copper sulphate anhydrous.;

69. The use according to any one of claims 57 to 63, wherein said formulation comprises up to 9% w/w copper chloride or up to 9% w/w copper salicylate.;

70. The use according to any one of claims 57 to 69, wherein said formulation comprises aloe vera.;RECEIVED at IPONZ on 10 October 2011;19;

71. The use of claim 7&>• WHereitf <saiFtf"' formulation comprises aloe vera at a concentration of 1% w/w of the formulation.;

72. The use according to any one of claims 57 to 71, wherein said formulation comprises sodium ascorbate.;

73. The use of claim 72, whereih* sMd fontrUiafion comprises sodium ascorbate at a concentration of 3% to 10% w/w of the formulation.

74. The use according to any one of claims 57 to 73, wherein said formulation comprises hydrogen peroxide.

75. The use of claim 74, wherein said formulation comprises hydrogen peroxide at a concentration of 3% to 10% w/w of the formulation.

76. The use according to any one of claims 57 to 75 further comprising a skin protectant.

77. The use of claim 76, wherein the skin protectant is present in the formulation at a concentration of 1% to 5% w/w.

78. The use of claim 76 or claim 77, wherein the skin protectant is glycerin.

79. The use according to any one of claims 57 to 78, wherein said composition further comprises any one or more of a preservative, osmotic regulator, thickener, flavor, fragrance, emollient, humectant, colorant, and/or pigment.

80. The use of claim 79, wherein the preservative is Germali Plus.

81. The use of claim 79 or claim 80, wherein the formulation comprises 0.1% to 0.3% w/w preservative.

82. Use of a composition comprising an effective amount of a copper compound and hypericum perforatum extract in the manufacture of a medicament for the topical treatment or prevention of viral associated skin and/or mucosal membrane lesions. RECEIVED at IPONZ on 10 October 2011 20

83. The use of claim 82, wherein the composition comprises a copper compound at a concentration of 5% to 9% w/w of the composition.

84. The use of claim 82 or claim 83, wherein the amount of copper compound provides a copper ion concentration at a range of 1% to 5% w/w of the composition.

85. The use of any one of claims 82 to 84, wherein the amount of copper compound provides copper ion at a concentration of 5% w/w of the composition.

86. The use according to any one of claims 82 to 85, wherein the copper compound is copper sulphate, copper chloride or copper salicylate.

87. The use according to claim 86, wherein the copper compound is copper sulphate.

88. The use according to claim 87, wherein the copper sulphate is copper sulphate pentahydrate.

89. The use according to any one of claims 86 to 88, wherein the copper sulphate is provided at a concentration of 7.8% (w/w) of the formulation.

90. The use according to claim 86 or claim 87, wherein the copper sulphate is copper sulphate anhydrous.

91. The use according to any one of claims 82 to 88 or claim 90, wherein said formulation comprises up to 7.8% w/w copper sulphate pentahydrate and/or up to 5,0% w/w copper sulphate anhydrous.

92. The use according to any one of claims 82 to 87, wherein said composition comprises up to 9% w/w copper chloride or up to 9% w/w copper salicylate.

93. The use according to any one of claims 82 to 91, wherein the hypericum perforatum extract is at a concentration range of 0.05% to 0.15% w/w of the composition.

94. The use according to any one of claims 82 to 93, wherein the hypericum perforatum extract is at a concentration of up to 0.2% v/v of the composition. RECEIVED at IPONZ on 10 October 2011 21

95. The use according to any one Of claims 82 to 94, wherein the composition further comprises a skin protectant

96. The use of'claim 95; wherein the skin protectant is present in the composition at a concentration of 1% to 5% w/w. ,

97. The use of Claim 35 fer Claim 96, wherein the skin protectant is glycerin.

98. The use according to any one of claims 82 to 92, where in the composition further comprises any One or more Of a preservative, osmotic regulator, thickener, flavor, fragrance, emollient, humectant, colorant, or pigment.

99. The use of claim 98, wherein the preservative is Germall Plus. »

100. The use of Cfaim 98 or claim 99, comprising 0.1% to 0.3% w/w preservative,

101. The use according to any one of claims 82 to 100, wherein the composition further comprises aloe vera.

102. The use of claim 101, wherein the composition comprises aloe vera at a concentration of 1% w/w of the composition.

103. The use composition according to any one of claims 82 to 102, wherein the composition further comprises sodium ascorbate.

104. The use of claim 103, wherein the composition comprises sodium ascorbate at a concentration of 3% to 10% w/w of the composition.

105. The use according any one of claims 82 to 104, wherein the composition further comprises hydrogen peroxide.

106. The use according to claim 105, wherein the composition comprises hydrogen peroxide at a concentration of 3% to 10% w/w of the composition. RECEIVED at IPONZ on 10 October 2011 22

107. The use according to nay one of claims 82 to 106, wherein the composition is in the form of a cream, lotioh, emollient, gel or emulsion.

108. The use according to any one of claims 57 to 107, wherein the viral infection is selected from the group consisting of Herpes Simplex virus, Herpes Zoster virus, Polio virus, Shingles-associated viruses, Varicella Zoster virus, Chicken pox-associated viruses or Human Immunodeficiency virus.

109. The use of claim 108, wherein the viral infection is caused by Herpes Simplex virus.

110. The process according to any one of claims 1 to 27, wherein the copper compound is a copper salt.

111. The composition according to any one of claims 28 to 55 as described herein with reference to any example hereof.

112. The use according to any one of claims 57 to 109 as described herein with reference to any example hereof,

113. The process according to any one of claims 1 to 27 or claim 56 or claim 110 as described herein with reference to any example hereof. Dated this SEVENTH day of OCTOBER 2011 Dynamiclear Pty Ltd, Patent Attorneys for the Applicant: F B RICE </div>